Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry has proven to be a useful analytical tool in the fields of proteomics and genomics. In these fields, MALDI has been used for protein identification and characterization, peptide fingerprinting, and DNA sequencing. Samples that are commonly analyzed using MALDI include peptides, proteins, polymers, oligonucleotides, oligosaccharides, tissue samples, and drugs.
Unfortunately, broader applications for MALDI mass spectrometry have been limited by the fact that detection sensitivity is restricted by sample handling and preparation techniques. Many of these limitations stem from the fact that current techniques for preparing sample spots on MALDI targets produce relatively large inhomogeneous sample spots. These large spots require a considerable amount of sample and often waste sample because only a small fraction of the sample spot is actually irradiated for ion generation during MALDI mass spectrometry. In addition, inhomogeneous sample spots may result in highly variable ion signals produced from a single sample spot.
The dried-droplet method is a well-known technique for creating sample spots on a MALDI target. In the dried-droplet method, a mixture of analyte and matrix solution is deposited in small volumes onto a MALDI target where a sample spot is left to dry and crystallize within a few minutes. The resulting sample spots are inhomogeneous spots having a spot size of about 4–5 mm2. Another technique commonly used to deposit sample spots on a MALDI target is electrospray deposition. In this technique, a small amount of matrix-analyte mixture is electrosprayed from a stainless-steel or glass capillary onto a grounded metal sample plate mounted a short distance away from the tip of the capillary. The spot size of sample spots deposited using electrospray deposition is typically about 100 μm or larger in diameter. Quill pen dispensation is another method for depositing sample spots on a MALDI target. Although quill pens have been used to produce sample spots having diameters as small as 75 micrometers using aqueous solutions, these pens are poorly suited for depositing small sample spots for MALDI applications because the saturated crystallized solutions used as matrix materials on a MALDI target tend to crystallize within and clog the quill pen tips.
More recently, attempts have been made to produce MALDI targets having small sample spots using piezoelectric microdispensers. Miliotis et al. have reported a method for producing MALDI targets using a piezoelectric microdispenser to apply sample spots to the target. Rapid Commun. Mass Spectrom., 2002, Vol. 16, pp. 117–126. However, even the reduced sample spot sizes achieved with these devices are typically at least 100 μm in diameter, and typically much larger. These larger spot sizes may be attributed to the mechanism of operation of the piezoelectric microdispensers, which relies on a cylindrical piezoelectric element surrounding a capillary to compress and expand the capillary, squeezing fluid from the capillary.
Meier et al. have reported the formation of a MALDI target using ink jet printing technology to deposit sample spots. Rapid Commun. Mass Spectrom., 2003, Vol. 17, pp. 2349–2353. The reported spot diameter for the ink jet printed sample spots was about 180–200 micrometers. However, due to problems with ink jet clogging, common MALDI solvents such as tetrahydrofuran and chloroform could not be used.
Thus, a need exists for a MALDI target composed of small homogeneous sample spots and methods for producing the same.